Anterior approach retroperitoneal laparoscopic renal surgery in children.

Retroperitoneoscopic renal surgery is performed by lateral or posterior approaches. Iterative modification led to development of an alternative 'anterior' approach. The study authors' experience with this novel approach in a prospective series of 69 children that includes 17 infants is reported. Mean operating time was 225 min for reduction pyeloplasty. Peritoneal tear is not uncommon (22%) but often does not require conversion. In the study authors' early experience, the conversion rate was 17% and postoperative complications 2.9%. This approach overcomes many existing challenges with retroperitoneoscopy. Benefits of exposure, orientation, and working space achieved with a transperitoneal approach are afforded while preserving the advantages of retroperitoneoscopy.

Association of type 2 diabetes with prolonged hospital stay and increased rate of readmission in patients with lower limb cellulitis.

BACKGROUND/AIMS: Lower limb (LL) cellulitis-related hospitalisations are prevalent in type 2 diabetes subjects. We assess its costs and factors associated with length of stay and readmissions. METHODS: A retrospective case-control study at an urban hospital servicing a multi-ethnic population in New Zealand, where 7% of the adult population is estimated to have diabetes. Admissions with LL cellulitis in 2008-2013 were identified using coding records. Subsequent hospitalisations after 1 month with the same diagnosis were classified as readmissions. Glycaemic control was assessed by HbA1c measured within 6 months of the index admission. RESULTS: There were 4600 admissions with LL cellulitis in 3636 patients, including 719 patients (20%) with type 2 diabetes. Hospital stay was longer for type 2 diabetes patients (median 5.3 vs 3.0 days, P < 0.001), independent of age, ethnicity and HbA1c. Accompanying LL ulceration was more frequent in type 2 diabetes patients (50% vs 17%, P < 0.001); however, admissions remained longer for type 2 diabetes patients without ulceration (median 3.4 vs 2.8 days, P < 0.001). Readmission rates were also higher in type 2 diabetes patients compared to non-diabetes patients (HR 1.7, P < 0.001), even in the absence of ulceration (HR 2.2, P < 0.001). Age, HbA1c and ethnicity did not distinguish those prone to readmissions in the type 2 diabetes cohort. Type 2 diabetes patients accounted for a fifth of all admissions and one third of the estimated costs. CONCLUSIONS: A high proportion of patients with type 2 diabetes was admitted with LL cellulitis. They had significantly longer admissions and higher readmission rates. Age, HbA1c and ethnicity did not predict length of stay or recurrence.

Fulminant type 1 diabetes in pregnancy.

We report two cases of fulminant type 1 diabetes in previously well migrants from South East Asia. This entity, which is rare outside East or South-East Asia, has a high perinatal mortality. The clinical presentation differs markedly from that of typical newly recognised type 1 diabetes in pregnancy. In both our cases, the neonates required intensive care but survived.

Does exposure to hyperglycaemia in utero increase the risk of obesity and diabetes in the offspring? A critical reappraisal.

BACKGROUND: The idea that exposure to hyperglycaemia in utero is an important factor in the development of obesity and diabetes in the offspring has become entrenched as popular belief. AIM: To appraise the literature supporting this hypothesis in the light of recent studies that have clarified the main drivers of obesity in children and adolescents. METHODS: A review of published evidence from animal studies, human observational studies, systematic reviews and experimental trials that address the impact of diabetes (Types 1 and 2, genetic or gestational) on the future risk of obesity and/or glucose intolerance in the offspring. RESULTS: Some animal studies support a relationship between exposure to hyperglycaemia in utero and future development of obesity and diabetes, but the results are inconsistent. Most of the human studies claiming to show a relationship have not taken into account important known confounders, such as maternal and paternal BMI. Evidence supporting a dose-response relationship between maternal hyperglycaemia exposure and obesity and diabetes in the offspring is weak, and there is no convincing evidence that treating gestational diabetes reduces the later risk of offspring obesity or glucose intolerance. CONCLUSIONS: Exposure to hyperglycaemia in utero has minimal direct effect on the later risk of obesity and Type 2 diabetes. The increased risk of obesity in the offspring of women with Type 2 or gestational diabetes can be explained by confounding factors, such as parental obesity.

Differing perceptions of intervention thresholds for fracture risk: a survey of patients and doctors.

UNLABELLED: This survey suggests that patients are prepared to accept higher absolute fracture risk than doctors, before considering pharmacological therapy to be justified. Patients require that drug treatments confer substantial fracture risk reductions in order to consider long-term therapy. INTRODUCTION: Absolute fracture risk estimates are now incorporated into osteoporosis treatment guidelines. At present, little is known about how patients regard fracture risk and its management. We set out to describe and compare the views of patients and doctors on the level of fracture risk at which drug treatment is justified. METHODS: A cross-sectional survey was conducted on 114 patients referred for bone density measurement and 161 doctors whose practice includes management of osteoporosis. Participants were asked about fracture risk thresholds for pharmacological intervention. RESULTS: The absolute risk of both major osteoporotic fracture and hip fracture at which drug treatment was considered by patients to be justifiable was higher than that reported by doctors [major osteoporotic fracture, median (interquartile range): patients, 50% (25 to 60); doctors, 10% (10 to 20); P < 0.0001; hip fracture: patients, 50% (25 to 60); doctors, 10% (5 to 20); P < 0.0001]. Patients required that a drug provide a median 50% reduction in relative risk of fracture in order to consider taking long-term therapy, irrespective of the treatment mode or dosing schedule. Among doctors, there was an inverse relationship between the number of osteoporosis consultations conducted each month and threshold of risk for recommending drug treatment (r = -0.22 and r = -0.29 for major osteoporotic fracture and hip fracture, respectively, P < 0.01 for both) CONCLUSIONS: Patients are prepared to accept higher absolute fracture risk than doctors, before considering pharmacological therapy to be justified. Patients require that drug treatments confer substantial fracture risk reductions in order to consider long-term therapy.

Proposed new diagnostic criteria for gestational diabetes--a pause for thought?

New criteria for the diagnosis of gestational diabetes promulgated by the International Association of Diabetes and Pregnancy Study Groups (IADSPG) have been adopted by a number of groups, including the American Diabetes Association. These criteria will increase two- to three-fold the number of women diagnosed with gestational diabetes and have enormous resource implications. The recommendations are derived from observations made in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, which demonstrated continuous relationships between maternal glucose tolerance and two clinically relevant outcomes of pregnancy (caesarean section rate and neonatal hypoglycaemia) and two surrogate measures (birth weight and cord C-peptide). The recent randomized intervention studies in mild gestational diabetes indicate that the major effects of detecting and treating mild gestational diabetes are a reduction in mean birthweight of 100-140 g, and a reduction in the incidence of shoulder dystocia. However, the women included in these studies were identified using different diagnostic criteria, and it cannot be assumed that women diagnosed by the less stringent IADSPG criteria will have the same benefit. Moreover, as the majority of cases of macrosomia and shoulder dystocia occur in women with normal glucose tolerance, the real impact of diagnosing many more 'cases' of gestational diabetes is likely to be minimal. The concentration on mild degrees of hyperglycaemia may well be misplaced, as most of the outcomes usually attributed to gestational diabetes are more strongly associated with maternal obesity and weight gain in pregnancy. The new testing procedure (with diagnosis based on a single blood glucose measurement) will inevitably be imprecise. Given the many reservations about the new criteria an urgent but dispassionate debate is required on the risks, costs and benefits of their introduction.

Severe intrauterine growth retardation and atypical diabetes associated with a translocation breakpoint disrupting regulation of the insulin-like growth factor 2 gene.

CONTEXT: IGF-II is an imprinted gene (predominantly transcribed from the paternally inherited allele), which has an important role in fetal growth in mice. IGF2 gene expression is regulated by a complex system of enhancers and promoters that determine tissue-specific and development-specific transcription. In mice, enhancers of the IGF2 gene are located up to 260 kb telomeric to the gene. The role of IGF-II in humans is unclear. OBJECTIVE: A woman of short adult stature (1.46 m, -3 sd score) born with severe intrauterine growth retardation (1.25 kg at term, -5.4 SD score) and atypical diabetes diagnosed at the age of 23 yr had a balanced chromosomal translocation t(1;11) (p36.22; p15.5). We hypothesized that her phenotype resulted from disruption of her paternally derived IGF2 gene because her daughter who inherited the identical translocation had normal birth weight. DESIGN: Both chromosomal break points were identified using fluorescent in situ hybridization. Sequence, methylation, and expression of the IGF2 gene was examined. Hyperinsulinemic, euglycemic clamp with glucose tracers and magnetic resonance imaging of the thorax, abdomen, and pelvis were performed. RESULTS: The 11p15.5 break point mapped 184 kb telomeric of the IGF2 gene. Microsatellite markers confirmed paternal origin of this chromosome. IGF2 gene sequence and methylation was normal. IGF2 gene expression was reduced in lymphoblasts. Clamp studies showed marked hepatic and total insulin resistance. Massive excess sc fat was seen on magnetic resonance imaging despite slim body mass index (21.1 kg/m2). CONCLUSIONS: A break point 184 kb upstream of the paternally derived IGF2 gene, separating it from some telomeric enhancers, resulted in reduced expression in some mesoderm-derived adult tissues causing intrauterine growth retardation, short stature, lactation failure, and insulin resistance with altered fat distribution.

Severe hypomagnesaemia in long-term users of proton-pump inhibitors.

OBJECTIVE: To explore the mechanism underlying severe hypomagnesaemia in long-term users of proton-pump inhibitors (PPIs). PATIENTS: Two cases of severe hypomagnesaemia in adult long-term users of the PPI omeprazole, presenting with hypocalcaemic seizures. MEASUREMENTS: We studied renal magnesium handling during an incremental intravenous magnesium infusion, and assessed total body magnesium status by the 24-h retention of the parenteral load. We also observed the effects of oral magnesium supplements whilst continuing the PPI, and the effect of withdrawal of the PPI. RESULTS: Both patients were severely magnesium-depleted and had avid renal magnesium retention, implicating a failure of intestinal magnesium absorption. There was no evidence of generalized malabsorption. The hypomagnesaemia could be partially corrected by high dose oral magnesium supplementation, and resolved on withdrawal of PPIs. CONCLUSIONS: PPI use can inhibit active magnesium transport in the intestine, though it is not clear if this is an idiosyncratic effect. Long-term PPI users who are highly adherent to treatment can eventually deplete total body magnesium stores and present with severe complications of hypomagnesaemia.

Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment.

Camurati-Engelmann disease (CED) is a rare autosomal dominant type of bone dysplasia. This review is based on the unpublished and detailed clinical, radiological, and molecular findings in 14 CED families, comprising 41 patients, combined with data from 10 other previously reported CED families. For all 100 cases, molecular evidence for CED was available, as a mutation was detected in TGFB1, the gene encoding transforming growth factor (TGF) beta1. Pain in the extremities was the most common clinical symptom, present in 68% of the patients. A waddling gait (48%), easy fatigability (44%), and muscle weakness (39%) were other important features. Radiological symptoms were not fully penetrant, with 94% of the patients showing the typical long bone involvement. A large percentage of the patients also showed involvement of the skull (54%) and pelvis (63%). The review provides an overview of possible treatments, diagnostic guidelines, and considerations for prenatal testing. The detailed description of such a large set of CED patients will be of value in establishing the correct diagnosis, genetic counselling, and treatment.

Lifetime risk of symptomatic carpal tunnel syndrome in Type 1 diabetes.

AIMS: To determine the lifetime risk of developing symptomatic carpal tunnel syndrome (CTS) in subjects with Type 1 diabetes and to investigate the effect of glycaemic control, body mass index (BMI), gender and age of onset of diabetes. METHODS: One hundred and twenty-two consecutive subjects with Type 1 diabetes seen by a single investigator, over 1-year, were questioned about previous surgery for, or current symptoms of CTS. Those with current symptoms were referred for nerve conduction studies (NCS). Those with previous surgery and/or diagnostic NCS were classified as having CTS. Lifetime risk was calculated by the Kaplan-Meier method. RESULTS: Twenty six out of 122 patients had CTS, 18 of whom (69%) had undergone median nerve decompression surgery. The predicted lifetime risk of CTS reached 85% after 54 years of Type 1 diabetes (95% confidence interval: 72-97%). The duration of diabetes was greater in those who had developed CTS than in those who had not (29 vs. 19 years, P=0.0001). In those diagnosed with diabetes before the age of 20 there was a lag time of at least 19 years before the development of CTS, whereas patients with later onset of diabetes, began to develop CTS from as early as 5 years diabetes duration. There was no demonstrable effect of glycaemic control, obesity, gender or retinopathy on the appearance of CTS. CONCLUSION: The lifetime risk of developing symptomatic CTS with Type 1 diabetes is high, and is related to age and duration of diabetes, but not to the development of microvascular complications.

Effects of once-weekly oral alendronate on bone in children on glucocorticoid treatment.

OBJECTIVES: To determine the effects of once-weekly oral alendronate on indices of bone size, density and resorption in children with chronic illness being treated with glucocorticoids. METHODS: Twenty-two children with chronic illness treated with prednisone were randomized to receive 1 year's treatment with either once-weekly oral placebo or alendronate (1-2 mg/kg body weight) in a double-blind study. The main outcome measures were changes in lumbar spine and femoral shaft size and volumetric density (measured by dual energy X-ray absorptiometry) and N-telopeptide excretion (a marker of bone resorption). RESULTS: Once-weekly alendronate was well tolerated, and there were no major adverse events. In both groups bone size and bone mineral content increased through growth. Volumetric bone density of the lumbar spine increased significantly in the alendronate group (P = 0.013), but not in the placebo group. There were no differences between the groups in growth in the cortical width of the femoral shaft, but the cross-sectional moment of inertia per unit length-a derived estimate of mechanical strength-increased significantly in the alendronate group (P = 0.014) but not in the placebo group. Urine N-telopeptide excretion was suppressed significantly in the alendronate group (P = 0.007) but not in the placebo group. Height velocity was positively correlated with changes in both lumbar spine area and the total width of the femoral shaft (P = 0.015, P = 0.026, respectively). CONCLUSION: Once-weekly oral alendronate is well tolerated, suppresses bone resorption and may improve volumetric bone density at the lumbar spine and mechanical strength of the femoral shaft in children with chronic illness taking glucocorticoids. It does not affect bone growth. Larger controlled studies are needed to determine if these changes translate into reduced fracture incidence or greater peak bone mass. This study highlights the importance of differentiating between changes in bone size and changes in volumetric bone density in assessing bone in children, and also having control subjects in intervention studies.